There is strong evidence that osteoclast (OC) is the principal cell type responsible for bone resorption in inflammatory joint diseases (Harris, 1990; Sakiyama et al., 2001; Sato and Takayanagi, 2006; Mundy, 2007). Rheumatoid arthritis (RA) is characterized by the presence of inflammatory synovitis accompanied by the destruction of the joint cartilage and bone (Harris, 1990; Mundy, 2007; Sugimura and Li, 2010). OCs are bone-resorbing cells that differentiate from hematopoietic precursors of the monocyte/macrophage lineage (Sakiyama et al., 2001; Boyce et al., 2007). OCs are multinuclear giant cells that stain positive for tartrate-resistant acid phosphatase (TRAP) and serine protease cathepsin K (CTSK) (Kiviranta et al., 2001; Boyce et al., 2007).
Monocyte chemotactic protein-1 (MCP-1), a CC chemokine commonly found at the site of tooth eruption, RA bone degradation, and bacterially induced bone loss (Wise et al., 2002), is known to induce differentiation of monocytes into TRAP and CTSK-positive precursors of OCs. MCP-1 is expressed by mature OCs and its expression is regulated by nuclear factor-κB (NF-κB) (Kim et al., 2005). Several reports showed that MCP-1 is induced by NF-κB ligand RANKL and promotes OC fusion into multinuclear TRAP-positive cells without bone-resorption activity (Kim et al., 2006a,b), which might be called OC precursors. Recently, it has been reported that MCP-1 plays an important role in regulating OC differentiation in an autocrine/paracrine manner under stimulation by RANKL (Miyamoto et al., 2009). How MCP-1 mediates OC differentiation remains unclear.
The cellular effect of MCP-1 is mediated by the CCR2, a G-protein-coupled receptor that is induced by the receptor activator of RANKL (Gerszten et al., 2001; Kim et al., 2005). The signaling process initiated by MCP-1 binding to CCR2 leads to changes in gene expression.
Recently, it was found that this MCP-1 binding leads to the induction of a novel zinc-finger protein called MCPIP in human peripheral blood monocytes (Zhou et al., 2006). The biological functions of MCPIP, however, remain poorly understood.